Study on the synergistic and attenuating mechanism of the combination of Epimedium and Ligustri lucidi fructus based on pharmacokinetics

Epimedium has a wide range of clinical applications; however, there have been numerous reports of adverse reactions in recent years, which has resulted in it being changed from a widely recognized “nontoxic” to a “potentially toxic” traditional Chinese medicine. The combination of Epimedium and Ligustri lucidi fructus is commonly used in the clinic. The purpose of this study was to investigate the pharmacokinetic characteristics of Epimedium and Ligustri lucidi fructus to explore the possible synergism and reduction in toxicity. Based on liquid chromatography tandem mass spectrometry, a method was established for the determination of icariin, epimedin A, epimedin B, epimedin C, baohuoside Ⅰ, and specnuezhenide in biological samples and was successfully applied to study the pharmacokinetics of the drug pair. The results showed that the five flavonoids (specnuezhenide could not be detected) could be rapidly absorbed into the blood, and the second peak time in vivo was earlier after the combination, indicating that the metabolic pathway may be changed. In addition, combination with Ligustri lucidi fructus could significantly reduce the concentration of 5 flavonoids in vivo and increase their elimination rate, which may attenuate their virulence, thus providing a reference for the rational clinical use of Epimedium .